Mechanisms of inflammation in the lung will be studied as they occur in response to inhaled mitogenic and antigenic substances. In previous work we have shown that T-cell mitogens (concanavallin A, phytohemagglutinin) induce a diffuse interstitial inflammation when inhaled by unsensitized rabbits. Animals possessing high titers of antibody manifest but minimal injury following aerosol challenge with specific antigens, but develop devastating inflammatory reactions following challenge with antigen plus mitogen. We propose that mitogen-induced pulmonary injury is mediated by lymphokines released from T-cells stimulated within the lung, and thus serves as a useful model for cell-mediated pulmonary disease. We wish to 1) test the validity of this hypothesis; 2) demonstrate the ability of lymphokines prepared in vitro to induce pulmonary inflammation directly; 3) define the role of cell-mediated inflammation in facilitating local immune-complex injury; 4) determine the ability of cyclic nucleotides to modify inflammatory lung disease; 5) induce pulmonary fibrosis through chronic interstitial irritation; and 6) related inflammatory lung disease in its acute and chronic forms to alterations in respiratory physiologic function.